Fondazione IFOM, Istituto FIRC di Oncologia Molecolare (IFOM-IEO Campus), Via Adamello 16, 20139 Milan, Italy.
Mol Cell. 2010 Aug 27;39(4):595-605. doi: 10.1016/j.molcel.2010.07.024.
Chromosome replication initiates at multiple replicons and terminates when forks converge. In E. coli, the Tus-TER complex mediates polar fork converging at the terminator region, and aberrant termination events challenge chromosome integrity and segregation. Since in eukaryotes, termination is less characterized, we used budding yeast to identify the factors assisting fork fusion at replicating chromosomes. Using genomic and mechanistic studies, we have identified and characterized 71 chromosomal termination regions (TERs). TERs contain fork pausing elements that influence fork progression and merging. The Rrm3 DNA helicase assists fork progression across TERs, counteracting the accumulation of X-shaped structures. The Top2 DNA topoisomerase associates at TERs in S phase, and G2/M facilitates fork fusion and prevents DNA breaks and genome rearrangements at TERs. We propose that in eukaryotes, replication fork barriers, Rrm3, and Top2 coordinate replication fork progression and fusion at TERs, thus counteracting abnormal genomic transitions.
染色体复制从多个复制起点起始，并在叉头汇聚时终止。在大肠杆菌中，Tus-TER 复合物介导终止子区域的极性叉头汇聚，而异常的终止事件会挑战染色体的完整性和分离。由于在真核生物中，终止过程的特征不太明确，我们利用芽殖酵母来鉴定在复制染色体上协助叉头融合的因素。通过基因组和机制研究，我们已经鉴定和描述了 71 个染色体终止区域 (TERs)。TERs 包含影响叉头推进和融合的叉头停顿元件。Rrm3 DNA 解旋酶协助叉头在 TER 上推进，抵消 X 形结构的积累。Top2 DNA 拓扑异构酶在 S 期与 TER 结合，G2/M 促进叉头融合，并防止 TER 处的 DNA 断裂和基因组重排。我们提出，在真核生物中，复制叉障碍、Rrm3 和 Top2 协调 TER 处的复制叉推进和融合，从而抵消异常的基因组转变。
